Benign Prostate Hypertrophy, Male Hypogonadism, Muscle Atrophy, Sarcopenia
Conditions
Keywords
anabolic effects, finasteride, male hypogonadism, sarcopenia, testosterone
Brief summary
The purpose of this study is to determine whether a higher-than-replacement dose of testosterone and finasteride can be combined to safely increase muscle strength in older men who have a low blood concentration of testosterone.
Detailed description
Approximately 40% of older male veterans have a low serum testosterone concentration. The latter is associated with diminished muscle strength and bone mineral density, depressed mood, low pain tolerance, frailty, and increased mortality. Replacement doses of testosterone have been administered to hypogonadal men for the purpose of reversing deficits in muscle and bone. Although testosterone is clearly important for maintaining muscle and bone in men, there are problems associated with T replacement. First, testosterone causes a number of undesired effects, including fluid retention, gynecomastia, worsening of sleep apnea, polycythemia, prostate enlargement and acceleration of early-stage prostate cancer. The anabolic effects obtained to date from testosterone replacement have been relatively modest, especially in older men. Our hypothesis is that combined treatment with a higher-than-replacement dose of testosterone and a 5- reductase inhibitor will produce substantial anabolic effects, while preventing testosterone-induced prostate enlargement and possibly other adverse effects. We plan to investigate the efficacy and safety of combined treatment with testosterone and finasteride in older hypogonadal male veterans by conducting a 12-month randomized, placebo-controlled trial. We will administer a higher-than-replacement dose of testosterone plus the 5- reductase inhibitor finasteride to a group of hypogonadal, but otherwise healthy older men. We will determine whether this treatment is a safe and effective means to increase muscle mass and strength. Men aged 60 to 80, with circulating total testosterone 300 ng/dL or bioavailable testosterone 70 ng/dL, will be treated with 125 mg testosterone enanthate/week 5 mg finasteride/day for 1 year. We will assess the effects on body composition, 1- repetition maximum (1-RM) strength, grip strength, functional reach, bone mineral density, mood, cognition, hematopoiesis and prostate volume. We have chosen a moderately high dose of testosterone that may cause some adverse effects. We predict that finasteride will not block the anabolic effects of testosterone, but will block any prostate enlargement or symptoms and possibly other adverse effects as well.
Interventions
DRUGTestosterone Enanthate
125 mg, i.m. injection, once/week, for 52 weeks
DRUGFinasteride
5 mg, oral, once/day, for 52 weeks
OTHERPlacebo
Placebo
Sponsors
Endo Pharmaceuticals
Merck Sharp & Dohme LLC
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
60 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Age \> 60 years males * Primary care at the Malcolm Randall VA Medical Center in Gainesville, Florida. * Consenting subjects who have a morning (between 6:00 AM and 10:00 AM) serum total testosterone 300 ng/dL or bioavailable testosterone concentration 70 ng/dL and no
Exclusion criteria
will be randomized to receive either testosterone or placebo.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1 Repetition Maximum (1-RM) Strength Testing | baseline, 3 months, 6 months, 9 months, 12 months | 1-RM strength testing for 5 exercises will be performed using dynamic resistance exercise machines. Testing will be performed before treatment (baseline), at 3, 6, 9 and 12 months after treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lumbar Spine L2-L4 Bone Mineral Density | baseline, 12 months | Dual x-ray absorptiometry (DXA): We will assess bone mineral density (BMD) and body composition using a fan-bean densitometer (Lunar Prodigy, General Electric Medical Systems). |
| Geriatric Depression Scale | baseline, 3 months, 6 months, 9 months, 12 months | Geriatric Depression Scale (GDS): This 15-item, yes/no questionnaire will be administered at baseline, after 3, 6, 9 and 12 months of treatment. The minimum score is 0 = no depressive symptoms The maximum score is 15 = a very high level of depressive symptoms |
| 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test | baseline, 3 months, 6 months, 9 months, 12 months | Rey Osterrieth Complex Figure (ROCF) test is a widely used standardized neuropsychological test for assessing visuospatial constructional functions, visuographic memory, and some aspects of planning. The drawing is scored by a blinded neuropsychologist on a scale of 0 to 30 with 30 representing a perfect drawing. |
| Trail-Making Test, Part A | baseline, 3 months, 6 months, 9 months, 12 months | Trail-Making Test, Part A: is a standardized test of cognitive function which specifically assesses working memory, visual processing, visual spatial skills, selective and divided attention, and psychomotor coordination. the test is scored as seconds required to successful completion of the task with a lower score representing better performance. The mean score on test is 30.75 second with a standard deviation of 16.27. |
| Grip Strength kg | baseline, 3 months, 6 months, 9 months, 12 months | Grip strength in the dominant arm will be measured by using a dynamometer. Testing will be performed at baseline, after 3, 6, 9 and 12 months of treatment. |
| Hematocrit | baseline, 3 months, 6 months, 9 months, 12 months | Hematocrit was assessed as a part of routine blood analysis at the indicated time points. |
| Dietary Protein Intake | baseline, 3 months, 6 months, 9 months, 12 months | Dietary protein intake will be assessed using a 3-day food log and subjects will be counseled to increase protein intake if needed using the guide Healthy Ways to Eat More Protein. |
| Transrectal Ultrasound Sizing of Prostate | baseline, 6 month, 12 months | Transrectal ultrasound sizing of prostate will be performed using the B&K Diagnostic System 3535, with 7 mega hertz transrectal probe at baseline and after 6 and 12 months of treatment. |
| Life Satisfaction | baseline, 3 months, 6 months, 9 months, 12 months | Life Satisfaction: is a written test of psychological well-being that will be performed at baseline, after 3, 6, 9 and 12 months of treatment. This is a 20-point scale, with a possible range of scores from 0 to 20. A higher score represents greater life satisfaction. |
| Benton Judgment of Line Orientation Test | baseline, 3 months, 6 months, 9 months, 12 months | Benton Judgment of Line Orientation Test is a standardized test with 30 items that is specific for visual spatial cognition. Tests will be administered at baseline, after 3, 6, 9 and 12 months of treatment. The minimum score is 0, indicating low visual spatial cognition. The maximum score is 30, indicating high visual spatial cognition |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited between 7/2/2007 and 10/13/2010. Subjects responded to letters mailed to male patients aged 60 years or more who were seen at VA clinics.
Pre-assignment details
Subjects were excluded if they failed brief cognitive testing (MiniCog), if serum testosterone \> 300 ng/dL or less and bio-testosterone \> 70 ng/dL, congestive heart failure, sleep apnea, hematocrit (HCT) \> 49%, prostate specific antigen (PSA) \> 2.6 ng/ml, were taking coumadin or had orthopedic limitations.
Participants by arm
| Arm | Count |
|---|---|
| Testosterone Vehicle 125 mg testosterone enanthate/week i.m. daily placebo pill | 14 |
| Vehicle Finasteride weekly vehicle injection 5 mg finasteride/day p.o. | 13 |
| Testosterone Finasteride 125 mg testosterone enanthate/week i.m. 5 mg finasteride/day p.o. | 17 |
| Vehicle Placebo weekly vehicle injection daily placebo pill | 16 |
| Total | 60 |
Baseline characteristics
| Characteristic | Testosterone Vehicle | Vehicle Finasteride | Testosterone Finasteride | Vehicle Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 69.2 years STANDARD_DEVIATION 8 | 69.5 years STANDARD_DEVIATION 9.2 | 64.2 years STANDARD_DEVIATION 4.8 | 70.8 years STANDARD_DEVIATION 9.7 | 68.25 years STANDARD_DEVIATION 8.29 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 14 Participants | 13 Participants | 17 Participants | 16 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 14 | 1 / 13 | 2 / 17 | 0 / 16 |
| serious Total, serious adverse events | 3 / 14 | 2 / 13 | 0 / 17 | 1 / 16 |
Outcome results
Primary
1 Repetition Maximum (1-RM) Strength Testing
1-RM strength testing for 5 exercises will be performed using dynamic resistance exercise machines. Testing will be performed before treatment (baseline), at 3, 6, 9 and 12 months after treatment.
Time frame: baseline, 3 months, 6 months, 9 months, 12 months
Population: per protocol
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 | 1 Repetition Maximum (1-RM) Strength Testing | leg press 9-months change kg | 14.416 kg | Standard Error 2.63 |
| Arm 1 | 1 Repetition Maximum (1-RM) Strength Testing | leg press 3-months change kg | 9.192 kg | Standard Error 1.978 |
| Arm 1 | 1 Repetition Maximum (1-RM) Strength Testing | leg press 12-months change kg | 14.773 kg | Standard Error 7.03 |
| Arm 1 | 1 Repetition Maximum (1-RM) Strength Testing | leg press 6-months change kg | 10.227 kg | Standard Error 1.66 |
| Arm 1 | 1 Repetition Maximum (1-RM) Strength Testing | leg press baseline Kg | 129.1 kg | Standard Error 9.08 |
| Arm 2 | 1 Repetition Maximum (1-RM) Strength Testing | leg press 6-months change kg | -1.136 kg | Standard Error 4.095 |
| Arm 2 | 1 Repetition Maximum (1-RM) Strength Testing | leg press 9-months change kg | -5.55 kg | Standard Error 4.95 |
| Arm 2 | 1 Repetition Maximum (1-RM) Strength Testing | leg press 12-months change kg | 0 kg | Standard Error 2.629 |
| Arm 2 | 1 Repetition Maximum (1-RM) Strength Testing | leg press 3-months change kg | -1.34 kg | Standard Error 3.126 |
| Arm 2 | 1 Repetition Maximum (1-RM) Strength Testing | leg press baseline Kg | 109.4 kg | Standard Error 7.87 |
| Arm 3 | 1 Repetition Maximum (1-RM) Strength Testing | leg press 6-months change kg | 13.778 kg | Standard Error 4.1 |
| Arm 3 | 1 Repetition Maximum (1-RM) Strength Testing | leg press baseline Kg | 137.2 kg | Standard Error 5.8 |
| Arm 3 | 1 Repetition Maximum (1-RM) Strength Testing | leg press 3-months change kg | 9.679 kg | Standard Error 3.16 |
| Arm 3 | 1 Repetition Maximum (1-RM) Strength Testing | leg press 9-months change kg | 10.49 kg | Standard Error 3.1 |
| Arm 3 | 1 Repetition Maximum (1-RM) Strength Testing | leg press 12-months change kg | 12.5 kg | Standard Error 3.88 |
| Arm 4 | 1 Repetition Maximum (1-RM) Strength Testing | leg press 9-months change kg | 2.02 kg | Standard Error 2.636 |
| Arm 4 | 1 Repetition Maximum (1-RM) Strength Testing | leg press 3-months change kg | -2.44 kg | Standard Error 2.22 |
| Arm 4 | 1 Repetition Maximum (1-RM) Strength Testing | leg press baseline Kg | 118.8 kg | Standard Error 8.825 |
| Arm 4 | 1 Repetition Maximum (1-RM) Strength Testing | leg press 6-months change kg | 2.727 kg | Standard Error 3.66 |
| Arm 4 | 1 Repetition Maximum (1-RM) Strength Testing | leg press 12-months change kg | 1.515 kg | Standard Error 3.47 |
Comparison: The studies was powered for 1-RM strength based on a 1.18-alpha increase reported in the literaturep-value: <0.00195% CI: [7.86, 18]Mixed Models Analysis
Secondary
30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test
Rey Osterrieth Complex Figure (ROCF) test is a widely used standardized neuropsychological test for assessing visuospatial constructional functions, visuographic memory, and some aspects of planning. The drawing is scored by a blinded neuropsychologist on a scale of 0 to 30 with 30 representing a perfect drawing.
Time frame: baseline, 3 months, 6 months, 9 months, 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 | 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test | Rey 9 month | 15.25 units on a scale | Standard Error 3.06 |
| Arm 1 | 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test | Rey 3 month | 16.68 units on a scale | Standard Error 2.25 |
| Arm 1 | 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test | Rey 12 month | 16.86 units on a scale | Standard Error 2.91 |
| Arm 1 | 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test | Rey 6 month | 15.76 units on a scale | Standard Error 2.6 |
| Arm 1 | 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test | Rey baseline | 12.42 units on a scale | Standard Error 1.46 |
| Arm 2 | 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test | Rey 6 month | 16.17 units on a scale | Standard Error 2.04 |
| Arm 2 | 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test | Rey 9 month | 15.17 units on a scale | Standard Error 2.27 |
| Arm 2 | 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test | Rey 12 month | 15 units on a scale | Standard Error 2.56 |
| Arm 2 | 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test | Rey 3 month | 12.85 units on a scale | Standard Error 1.57 |
| Arm 2 | 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test | Rey baseline | 13.54 units on a scale | Standard Error 1.36 |
| Arm 3 | 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test | Rey 6 month | 17.38 units on a scale | Standard Error 1.55 |
| Arm 3 | 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test | Rey baseline | 12.82 units on a scale | Standard Error 0.92 |
| Arm 3 | 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test | Rey 3 month | 16.27 units on a scale | Standard Error 1.6 |
| Arm 3 | 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test | Rey 9 month | 18.08 units on a scale | Standard Error 1.39 |
| Arm 3 | 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test | Rey 12 month | 19.27 units on a scale | Standard Error 1.98 |
| Arm 4 | 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test | Rey 9 month | 15.55 units on a scale | Standard Error 2.45 |
| Arm 4 | 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test | Rey 3 month | 12.5 units on a scale | Standard Error 1.5 |
| Arm 4 | 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test | Rey baseline | 12.8 units on a scale | Standard Error 1.58 |
| Arm 4 | 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test | Rey 6 month | 14 units on a scale | Standard Error 2.7 |
| Arm 4 | 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test | Rey 12 month | 16.45 units on a scale | Standard Error 2.77 |
Comparison: The study was not powered for 30-minute recall on Rey figure testp-value: 0.01295% CI: [0.699, 5.04]Mixed Models Analysis
Secondary
Benton Judgment of Line Orientation Test
Benton Judgment of Line Orientation Test is a standardized test with 30 items that is specific for visual spatial cognition. Tests will be administered at baseline, after 3, 6, 9 and 12 months of treatment. The minimum score is 0, indicating low visual spatial cognition. The maximum score is 30, indicating high visual spatial cognition
Time frame: baseline, 3 months, 6 months, 9 months, 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 | Benton Judgment of Line Orientation Test | Benton 9 months | 25.38 units on a scale | Standard Error 1.48 |
| Arm 1 | Benton Judgment of Line Orientation Test | Benton 3 months | 25.00 units on a scale | Standard Error 0.73 |
| Arm 1 | Benton Judgment of Line Orientation Test | Benton 12 months | 25.67 units on a scale | Standard Error 0.8 |
| Arm 1 | Benton Judgment of Line Orientation Test | Benton 6 months | 25.90 units on a scale | Standard Error 1.18 |
| Arm 1 | Benton Judgment of Line Orientation Test | Benton baseline | 24.54 units on a scale | Standard Error 1.26 |
| Arm 2 | Benton Judgment of Line Orientation Test | Benton 6 months | 25.11 units on a scale | Standard Error 1.33 |
| Arm 2 | Benton Judgment of Line Orientation Test | Benton 9 months | 23.89 units on a scale | Standard Error 1.23 |
| Arm 2 | Benton Judgment of Line Orientation Test | Benton 12 months | 25.5 units on a scale | Standard Error 1.12 |
| Arm 2 | Benton Judgment of Line Orientation Test | Benton 3 months | 25.40 units on a scale | Standard Error 1.38 |
| Arm 2 | Benton Judgment of Line Orientation Test | Benton baseline | 24.39 units on a scale | Standard Error 0.8 |
| Arm 3 | Benton Judgment of Line Orientation Test | Benton 6 months | 26.0 units on a scale | Standard Error 0.79 |
| Arm 3 | Benton Judgment of Line Orientation Test | Benton baseline | 25.88 units on a scale | Standard Error 0.92 |
| Arm 3 | Benton Judgment of Line Orientation Test | Benton 3 months | 25.07 units on a scale | Standard Error 1.09 |
| Arm 3 | Benton Judgment of Line Orientation Test | Benton 9 months | 25.79 units on a scale | Standard Error 0.81 |
| Arm 3 | Benton Judgment of Line Orientation Test | Benton 12 months | 26.17 units on a scale | Standard Error 0.77 |
| Arm 4 | Benton Judgment of Line Orientation Test | Benton 9 months | 24.92 units on a scale | Standard Error 1.75 |
| Arm 4 | Benton Judgment of Line Orientation Test | Benton 3 months | 25.67 units on a scale | Standard Error 1.17 |
| Arm 4 | Benton Judgment of Line Orientation Test | Benton baseline | 24.69 units on a scale | Standard Error 1.23 |
| Arm 4 | Benton Judgment of Line Orientation Test | Benton 6 months | 25.08 units on a scale | Standard Error 1.26 |
| Arm 4 | Benton Judgment of Line Orientation Test | Benton 12 months | 24.08 units on a scale | Standard Error 1.88 |
Comparison: The study was not powered for score on Benton testp-value: 0.43395% CI: [-0.869, 2.043]Mixed Models Analysis
Secondary
Dietary Protein Intake
Dietary protein intake will be assessed using a 3-day food log and subjects will be counseled to increase protein intake if needed using the guide Healthy Ways to Eat More Protein.
Time frame: baseline, 3 months, 6 months, 9 months, 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 | Dietary Protein Intake | protein intake 9 months | 1.15 gm/body weight (kg) | Standard Error 0.08 |
| Arm 1 | Dietary Protein Intake | protein intake 3 months | 0.87 gm/body weight (kg) | Standard Error 0.16 |
| Arm 1 | Dietary Protein Intake | protein intake 12 months n = 1,1,2,5 | 1.18 gm/body weight (kg) | — |
| Arm 1 | Dietary Protein Intake | protein intake 6 months | 0.74 gm/body weight (kg) | Standard Error 0.07 |
| Arm 1 | Dietary Protein Intake | protein intake baseline | 0.97 gm/body weight (kg) | Standard Error 0.1 |
| Arm 2 | Dietary Protein Intake | protein intake 6 months | 1.27 gm/body weight (kg) | Standard Error 0.49 |
| Arm 2 | Dietary Protein Intake | protein intake 9 months | 1.20 gm/body weight (kg) | Standard Error 0.3 |
| Arm 2 | Dietary Protein Intake | protein intake 12 months n = 1,1,2,5 | 0.74 gm/body weight (kg) | — |
| Arm 2 | Dietary Protein Intake | protein intake 3 months | 0.94 gm/body weight (kg) | Standard Error 0.15 |
| Arm 2 | Dietary Protein Intake | protein intake baseline | 1.06 gm/body weight (kg) | Standard Error 0.08 |
| Arm 3 | Dietary Protein Intake | protein intake 6 months | 1.05 gm/body weight (kg) | Standard Error 0.18 |
| Arm 3 | Dietary Protein Intake | protein intake baseline | 0.99 gm/body weight (kg) | Standard Error 0.13 |
| Arm 3 | Dietary Protein Intake | protein intake 3 months | 1.49 gm/body weight (kg) | Standard Error 0.18 |
| Arm 3 | Dietary Protein Intake | protein intake 9 months | 1.26 gm/body weight (kg) | Standard Error 0.3 |
| Arm 3 | Dietary Protein Intake | protein intake 12 months n = 1,1,2,5 | 1.39 gm/body weight (kg) | Standard Error 0.6 |
| Arm 4 | Dietary Protein Intake | protein intake 9 months | 0.82 gm/body weight (kg) | Standard Error 0.09 |
| Arm 4 | Dietary Protein Intake | protein intake 3 months | 1.12 gm/body weight (kg) | Standard Error 0.16 |
| Arm 4 | Dietary Protein Intake | protein intake baseline | 1.00 gm/body weight (kg) | Standard Error 0.06 |
| Arm 4 | Dietary Protein Intake | protein intake 6 months | 0.93 gm/body weight (kg) | Standard Error 0.18 |
| Arm 4 | Dietary Protein Intake | protein intake 12 months n = 1,1,2,5 | 1.05 gm/body weight (kg) | Standard Error 0.18 |
Comparison: The study was not powered for dietary protein intakep-value: 0.621995% CI: [-0.353, 6.37]Mixed Models Analysis
Secondary
Geriatric Depression Scale
Geriatric Depression Scale (GDS): This 15-item, yes/no questionnaire will be administered at baseline, after 3, 6, 9 and 12 months of treatment. The minimum score is 0 = no depressive symptoms The maximum score is 15 = a very high level of depressive symptoms
Time frame: baseline, 3 months, 6 months, 9 months, 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 | Geriatric Depression Scale | depression 9 months | 0.88 units on a scale | Standard Error 0.23 |
| Arm 1 | Geriatric Depression Scale | depression 3 months | 1.80 units on a scale | Standard Error 0.49 |
| Arm 1 | Geriatric Depression Scale | depression 12 months | 3.33 units on a scale | Standard Error 1.38 |
| Arm 1 | Geriatric Depression Scale | depression 6 months | 1.5 units on a scale | Standard Error 0.48 |
| Arm 1 | Geriatric Depression Scale | depression baseline | 2.38 units on a scale | Standard Error 0.49 |
| Arm 2 | Geriatric Depression Scale | depression 6 months | 2.22 units on a scale | Standard Error 1.3 |
| Arm 2 | Geriatric Depression Scale | depression 9 months | 1.89 units on a scale | Standard Error 0.99 |
| Arm 2 | Geriatric Depression Scale | depression 12 months | 2.88 units on a scale | Standard Error 1.42 |
| Arm 2 | Geriatric Depression Scale | depression 3 months | 2.90 units on a scale | Standard Error 1.24 |
| Arm 2 | Geriatric Depression Scale | depression baseline | 3.08 units on a scale | Standard Error 1.09 |
| Arm 3 | Geriatric Depression Scale | depression 6 months | 5.0 units on a scale | Standard Error 1.33 |
| Arm 3 | Geriatric Depression Scale | depression baseline | 4.93 units on a scale | Standard Error 2.76 |
| Arm 3 | Geriatric Depression Scale | depression 3 months | 3.23 units on a scale | Standard Error 0.86 |
| Arm 3 | Geriatric Depression Scale | depression 9 months | 3.69 units on a scale | Standard Error 1.07 |
| Arm 3 | Geriatric Depression Scale | depression 12 months | 3.73 units on a scale | Standard Error 1.18 |
| Arm 4 | Geriatric Depression Scale | depression 9 months | 2.92 units on a scale | Standard Error 0.94 |
| Arm 4 | Geriatric Depression Scale | depression 3 months | 1.67 units on a scale | Standard Error 0.3 |
| Arm 4 | Geriatric Depression Scale | depression baseline | 2.13 units on a scale | Standard Error 0.48 |
| Arm 4 | Geriatric Depression Scale | depression 6 months | 1.62 units on a scale | Standard Error 0.5 |
| Arm 4 | Geriatric Depression Scale | depression 12 months | 1.83 units on a scale | Standard Error 0.373 |
Comparison: The study is was not powered for score on Geriatric Depression Scalep-value: 0.03795% CI: [-1.41, -0.064]Mixed Models Analysis
Secondary
Grip Strength kg
Grip strength in the dominant arm will be measured by using a dynamometer. Testing will be performed at baseline, after 3, 6, 9 and 12 months of treatment.
Time frame: baseline, 3 months, 6 months, 9 months, 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 | Grip Strength kg | change grip strength 6 month kg | 2.02 kg | Standard Error 0.482 |
| Arm 1 | Grip Strength kg | change grip strength 12 month kg | 1.909 kg | Standard Error 0.249 |
| Arm 1 | Grip Strength kg | grip strength baseline kg | 17.0 kg | Standard Error 1.23 |
| Arm 1 | Grip Strength kg | change grip strength 9 month kg | 1.558 kg | Standard Error 0.505 |
| Arm 1 | Grip Strength kg | change grip strength 3 month kg | 1.66 kg | Standard Error 0.427 |
| Arm 2 | Grip Strength kg | change grip strength 6 month kg | 0.812 kg | Standard Error 1.357 |
| Arm 2 | Grip Strength kg | change grip strength 3 month kg | -0.045 kg | Standard Error 0.485 |
| Arm 2 | Grip Strength kg | change grip strength 12 month kg | 1.477 kg | Standard Error 0.211 |
| Arm 2 | Grip Strength kg | grip strength baseline kg | 16.9 kg | Standard Error 1.28 |
| Arm 2 | Grip Strength kg | change grip strength 9 month kg | 1.25 kg | Standard Error 0.555 |
| Arm 3 | Grip Strength kg | change grip strength 3 month kg | 0.485 kg | Standard Error 0.447 |
| Arm 3 | Grip Strength kg | change grip strength 12 month kg | 1.174 kg | Standard Error 0.302 |
| Arm 3 | Grip Strength kg | change grip strength 9 month kg | 1.331 kg | Standard Error 0.399 |
| Arm 3 | Grip Strength kg | change grip strength 6 month kg | 1.00 kg | Standard Error 0.589 |
| Arm 3 | Grip Strength kg | grip strength baseline kg | 18.2 kg | Standard Error 0.513 |
| Arm 4 | Grip Strength kg | change grip strength 12 month kg | 0.72 kg | Standard Error 0.342 |
| Arm 4 | Grip Strength kg | grip strength baseline kg | 17.472 kg | Standard Error 0.8522 |
| Arm 4 | Grip Strength kg | change grip strength 3 month kg | 0.212 kg | Standard Error 0.44 |
| Arm 4 | Grip Strength kg | change grip strength 6 month kg | -0.035 kg | Standard Error 0.411 |
| Arm 4 | Grip Strength kg | change grip strength 9 month kg | 0.152 kg | Standard Error 0.415 |
Comparison: The study was not powered on grip strength. We employed 2x2 analysis to determine effects of testosterone, finasteride and interaction.p-value: 0.01595% CI: [0.16, 1.31]Mixed Models Analysis
Secondary
Hematocrit
Hematocrit was assessed as a part of routine blood analysis at the indicated time points.
Time frame: baseline, 3 months, 6 months, 9 months, 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 | Hematocrit | change hematocrit 9 months % | 4.071 % volume | Standard Error 1.303 |
| Arm 1 | Hematocrit | change hematocrit 3 months % | 3.6 % volume | Standard Error 1.007 |
| Arm 1 | Hematocrit | change hematocrit 12 months % | 5.22 % volume | Standard Error 0.8498 |
| Arm 1 | Hematocrit | change hematocrit 6 months % | 4.044 % volume | Standard Error 0.94 |
| Arm 1 | Hematocrit | hematocrit baseline % | 42.6 % volume | Standard Error 0.833 |
| Arm 2 | Hematocrit | change hematocrit 6 months % | 0.557 % volume | Standard Error 0.758 |
| Arm 2 | Hematocrit | change hematocrit 9 months % | 0.63 % volume | Standard Error 1.36 |
| Arm 2 | Hematocrit | change hematocrit 12 months % | -1.175 % volume | Standard Error 0.984 |
| Arm 2 | Hematocrit | change hematocrit 3 months % | 0.611 % volume | Standard Error 1.143 |
| Arm 2 | Hematocrit | hematocrit baseline % | 41.2 % volume | Standard Error 1.042 |
| Arm 3 | Hematocrit | change hematocrit 6 months % | 4.331 % volume | Standard Error 0.7264 |
| Arm 3 | Hematocrit | hematocrit baseline % | 42.0 % volume | Standard Error 0.7 |
| Arm 3 | Hematocrit | change hematocrit 3 months % | 4.593 % volume | Standard Error 0.627 |
| Arm 3 | Hematocrit | change hematocrit 9 months % | 3.38 % volume | Standard Error 0.6622 |
| Arm 3 | Hematocrit | change hematocrit 12 months % | 4.173 % volume | Standard Error 0.8498 |
| Arm 4 | Hematocrit | change hematocrit 9 months % | -0.155 % volume | Standard Error 0.52 |
| Arm 4 | Hematocrit | change hematocrit 3 months % | -0.06 % volume | Standard Error 0.44 |
| Arm 4 | Hematocrit | hematocrit baseline % | 40.3 % volume | Standard Error 0.975 |
| Arm 4 | Hematocrit | change hematocrit 6 months % | 0.514 % volume | Standard Error 0.396 |
| Arm 4 | Hematocrit | change hematocrit 12 months % | -0.192 % volume | Standard Error 0.667 |
Comparison: This study was powered for hematocrit based on literature report that testosterone \> 2 alpha increase in hematocritp-value: <0.00195% CI: [3.07, 5.18]Mixed Models Analysis
Secondary
Life Satisfaction
Life Satisfaction: is a written test of psychological well-being that will be performed at baseline, after 3, 6, 9 and 12 months of treatment. This is a 20-point scale, with a possible range of scores from 0 to 20. A higher score represents greater life satisfaction.
Time frame: baseline, 3 months, 6 months, 9 months, 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 | Life Satisfaction | Life Satisfaction A 9 months | 14.75 points | Standard Error 1.03 |
| Arm 1 | Life Satisfaction | Life Satisfaction A 3 months | 12.67 points | Standard Error 0.76 |
| Arm 1 | Life Satisfaction | Life Satisfaction A 12 months | 15.17 points | Standard Error 1.11 |
| Arm 1 | Life Satisfaction | Life Satisfaction A 6 months | 13.70 points | Standard Error 1.05 |
| Arm 1 | Life Satisfaction | Life Satisfaction A baseline | 13.83 points | Standard Error 1.01 |
| Arm 2 | Life Satisfaction | Life Satisfaction A 6 months | 14.44 points | Standard Error 1.65 |
| Arm 2 | Life Satisfaction | Life Satisfaction A 9 months | 13.44 points | Standard Error 1.39 |
| Arm 2 | Life Satisfaction | Life Satisfaction A 12 months | 12.5 points | Standard Error 1.91 |
| Arm 2 | Life Satisfaction | Life Satisfaction A 3 months | 12.11 points | Standard Error 2 |
| Arm 2 | Life Satisfaction | Life Satisfaction A baseline | 12.08 points | Standard Error 1.65 |
| Arm 3 | Life Satisfaction | Life Satisfaction A 6 months | 11.20 points | Standard Error 1.59 |
| Arm 3 | Life Satisfaction | Life Satisfaction A baseline | 11.35 points | Standard Error 1.11 |
| Arm 3 | Life Satisfaction | Life Satisfaction A 3 months | 12.27 points | Standard Error 1.33 |
| Arm 3 | Life Satisfaction | Life Satisfaction A 9 months | 11.57 points | Standard Error 1.35 |
| Arm 3 | Life Satisfaction | Life Satisfaction A 12 months | 12.17 points | Standard Error 1.8 |
| Arm 4 | Life Satisfaction | Life Satisfaction A 9 months | 13.17 points | Standard Error 1.48 |
| Arm 4 | Life Satisfaction | Life Satisfaction A 3 months | 14.13 points | Standard Error 0.91 |
| Arm 4 | Life Satisfaction | Life Satisfaction A baseline | 12.69 points | Standard Error 1.08 |
| Arm 4 | Life Satisfaction | Life Satisfaction A 6 months | 13.54 points | Standard Error 1.26 |
| Arm 4 | Life Satisfaction | Life Satisfaction A 12 months | 13.83 points | Standard Error 1.38 |
Comparison: The study was not powered for score on Lif Satisfaction A testp-value: 0.19695% CI: [-3.434, 1.698]Mixed Models Analysis
Secondary
Lumbar Spine L2-L4 Bone Mineral Density
Dual x-ray absorptiometry (DXA): We will assess bone mineral density (BMD) and body composition using a fan-bean densitometer (Lunar Prodigy, General Electric Medical Systems).
Time frame: baseline, 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 | Lumbar Spine L2-L4 Bone Mineral Density | L2-L4 spine BMD baseline gm/cc | 1.03 gm/cc | Standard Error 0.041 |
| Arm 1 | Lumbar Spine L2-L4 Bone Mineral Density | change L2-L4 spine BMD 12 month gm/cc | 0.049 gm/cc | Standard Error 0.017 |
| Arm 2 | Lumbar Spine L2-L4 Bone Mineral Density | change L2-L4 spine BMD 12 month gm/cc | 0.002 gm/cc | Standard Error 0.006 |
| Arm 2 | Lumbar Spine L2-L4 Bone Mineral Density | L2-L4 spine BMD baseline gm/cc | 1.02 gm/cc | Standard Error 0.032 |
| Arm 3 | Lumbar Spine L2-L4 Bone Mineral Density | L2-L4 spine BMD baseline gm/cc | 0.99 gm/cc | Standard Error 0.0167 |
| Arm 3 | Lumbar Spine L2-L4 Bone Mineral Density | change L2-L4 spine BMD 12 month gm/cc | 0.053 gm/cc | Standard Error 0.017 |
| Arm 4 | Lumbar Spine L2-L4 Bone Mineral Density | L2-L4 spine BMD baseline gm/cc | 1.07 gm/cc | Standard Error 0.045 |
| Arm 4 | Lumbar Spine L2-L4 Bone Mineral Density | change L2-L4 spine BMD 12 month gm/cc | -0.020 gm/cc | Standard Error 0.011 |
Comparison: The study was not powered on lumbar spine bone mineral density. We employed a 2x2 analysis for effects ot testosterone, finasteride and interactionp-value: <0.00195% CI: [1.95, 6.43]Mixed Models Analysis
Secondary
Trail-Making Test, Part A
Trail-Making Test, Part A: is a standardized test of cognitive function which specifically assesses working memory, visual processing, visual spatial skills, selective and divided attention, and psychomotor coordination. the test is scored as seconds required to successful completion of the task with a lower score representing better performance. The mean score on test is 30.75 second with a standard deviation of 16.27.
Time frame: baseline, 3 months, 6 months, 9 months, 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 | Trail-Making Test, Part A | Trails A 9 months | 31.0 sec | Standard Error 4.48 |
| Arm 1 | Trail-Making Test, Part A | Trails A 3 months | 38.5 sec | Standard Error 5.24 |
| Arm 1 | Trail-Making Test, Part A | Trails A 12 months | 29.17 sec | Standard Error 6.47 |
| Arm 1 | Trail-Making Test, Part A | Trails A 6 months | 32.9 sec | Standard Error 3.91 |
| Arm 1 | Trail-Making Test, Part A | Trails A baseline | 37.59 sec | Standard Error 3.58 |
| Arm 2 | Trail-Making Test, Part A | Trails A 6 months | 39.0 sec | Standard Error 5.55 |
| Arm 2 | Trail-Making Test, Part A | Trails A 9 months | 38.56 sec | Standard Error 4.37 |
| Arm 2 | Trail-Making Test, Part A | Trails A 12 months | 40.0 sec | Standard Error 5.48 |
| Arm 2 | Trail-Making Test, Part A | Trails A 3 months | 42.1 sec | Standard Error 5.59 |
| Arm 2 | Trail-Making Test, Part A | Trails A baseline | 46.42 sec | Standard Error 3.61 |
| Arm 3 | Trail-Making Test, Part A | Trails A 6 months | 31.2 sec | Standard Error 2.1 |
| Arm 3 | Trail-Making Test, Part A | Trails A baseline | 36.65 sec | Standard Error 2.24 |
| Arm 3 | Trail-Making Test, Part A | Trails A 3 months | 33.53 sec | Standard Error 1.83 |
| Arm 3 | Trail-Making Test, Part A | Trails A 9 months | 29.07 sec | Standard Error 1.73 |
| Arm 3 | Trail-Making Test, Part A | Trails A 12 months | 32.5 sec | Standard Error 2.98 |
| Arm 4 | Trail-Making Test, Part A | Trails A 9 months | 43.17 sec | Standard Error 12.97 |
| Arm 4 | Trail-Making Test, Part A | Trails A 3 months | 44.33 sec | Standard Error 7.12 |
| Arm 4 | Trail-Making Test, Part A | Trails A baseline | 44.0 sec | Standard Error 6.76 |
| Arm 4 | Trail-Making Test, Part A | Trails A 6 months | 36.92 sec | Standard Error 5.21 |
| Arm 4 | Trail-Making Test, Part A | Trails A 12 months | 43.75 sec | Standard Error 13.26 |
Comparison: The study was not powered for score on Trials A testp-value: 0.77995% CI: [-5.095, 3.811]Mixed Models Analysis
Secondary
Transrectal Ultrasound Sizing of Prostate
Transrectal ultrasound sizing of prostate will be performed using the B&K Diagnostic System 3535, with 7 mega hertz transrectal probe at baseline and after 6 and 12 months of treatment.
Time frame: baseline, 6 month, 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 | Transrectal Ultrasound Sizing of Prostate | postate volume baseline cc | 26.4 cc | Standard Error 2.33 |
| Arm 1 | Transrectal Ultrasound Sizing of Prostate | change prostate volume 12 months cc | 11.42 cc | Standard Error 3.9 |
| Arm 1 | Transrectal Ultrasound Sizing of Prostate | change prostate volume 6 months cc | 7.626 cc | Standard Error 1.703 |
| Arm 2 | Transrectal Ultrasound Sizing of Prostate | postate volume baseline cc | 29.7 cc | Standard Error 3.395 |
| Arm 2 | Transrectal Ultrasound Sizing of Prostate | change prostate volume 12 months cc | -4.93 cc | Standard Error 3.3 |
| Arm 2 | Transrectal Ultrasound Sizing of Prostate | change prostate volume 6 months cc | -1.984 cc | Standard Error 4.31 |
| Arm 3 | Transrectal Ultrasound Sizing of Prostate | change prostate volume 6 months cc | -3.927 cc | Standard Error 2.25 |
| Arm 3 | Transrectal Ultrasound Sizing of Prostate | postate volume baseline cc | 37.1 cc | Standard Error 4.379 |
| Arm 3 | Transrectal Ultrasound Sizing of Prostate | change prostate volume 12 months cc | -1.72 cc | Standard Error 1.596 |
| Arm 4 | Transrectal Ultrasound Sizing of Prostate | postate volume baseline cc | 36.9 cc | Standard Error 3.9 |
| Arm 4 | Transrectal Ultrasound Sizing of Prostate | change prostate volume 12 months cc | -2.891 cc | Standard Error 2.57 |
| Arm 4 | Transrectal Ultrasound Sizing of Prostate | change prostate volume 6 months cc | -1.474 cc | Standard Error 3.147 |
Comparison: The study was powered for prostate volume based on a literature report that testosterone increases prostate volume 1.85 alpha per year. We employed a 2x2 analysis for effects of testosterone, finasteride and interaction.p-value: 0.005195% CI: [1.73, 8.94]Mixed Models Analysis